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1.
Open Forum Infect Dis ; 7(11): ofaa175, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33204743

RESUMO

We report a case of chronic hepatosplenic aspergillosis following immune reconstitution complicating colic aspergillosis in an AIDS patient with multicentric Castleman disease. Symptoms mimicked the clinical presentation of chronic disseminated candidiasis and responded to corticosteroid. This emerging entity enlarges the spectrum of fungal immune reconstitution inflammatory syndrome in the HIV setting.

2.
Int J Antimicrob Agents ; 56(3): 106083, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32659465

RESUMO

Systemic use of voriconazole (VCZ) might be restricted by adverse events, such as hepatotoxicity and neurotoxicity, or drug-drug interactions. Topical VCZ application to skin may help to treat local infection more effectively and limit unwanted whole-body exposure. Topical VCZ cream was stable for 90 days when refrigerated. A patient with cutaneous Fusarium solani infection on his right forearm was successfully treated with topical 1% VCZ cream after failure of oral VCZ treatment.

4.
Transpl Infect Dis ; 22(4): e13263, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32056348

RESUMO

Cryptococcal meningitis is a severe cause of central nervous system infections among immunocompromised solid organ transplant (SOT) patients. While new diagnostic methods as multiplex meningitis/encephalitis (ME) NAT (nucleic acid test) are increasingly used as a first-line tool in hospital practice, data in HIV-negative patients including SOT remain scarce. We report here false-negative results of multiplex NAT among SOT patients with proven cryptococcal meningitis.

5.
Eur J Pediatr ; 179(8): 1247-1254, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32080759

RESUMO

P. aeruginosa bloodstream infection (BSI) is associated with high hospital mortality. Empirical combination therapy is commonly used, but its benefit remains debated. The purpose of this study was to describe in a paediatric population, demographical characteristics and outcome of children treated for P. aeruginosa BSI receiving either a combined or single antibacterial therapy. We performed a retrospective, single-centre, cohort study of hospitalized children with P. aeruginosa BSI from 2007 to 2015. A total of 118 bloodstream infections (BSI) were analysed (102 (86.4%) hospital-acquired, including 52 (44.1%) hospitalized in intensive care unit). In immunocompromised children, 52% of BSI episodes were recorded. Recent medical history revealed that 68% were hospitalized, 31% underwent surgery and 67% had a prior antibiotic therapy within the last 3 months. In-hospital mortality was similar for patients receiving single or combined anti-Pseudomonas therapy (p = 0.78). In multivariate analysis, independent risk factors for in-hospital mortality were neutropenia (OR = 6.23 [1.94-20.01], hospitalization in ICU (OR = 5.24 [2.04-13.49]) and urinary tract infection (OR = 4.40 [1.02-19.25]).Conclusion: P. aeruginosa BSI mainly occurred in immunocompromised children. Most infections were hospital-acquired and associated with high mortality. Combination therapy did not improve survival. What is Known: • P. aeruginosa bloodstream infection (BSI) is associated with high hospital mortality. Empirical combination therapy is commonly used but its benefit remains debated. What is New: • This is the largest cohort of Pseudomonas aeruginosa bacteraemia in children ever published. P. aeruginosa Bloodstream mainly occurred in immunocompromised children. Most infections were hospital-acquired and associated with high mortality. Combination therapy did not improve survival.

6.
Clin Infect Dis ; 71(4): 1106-1119, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31900476

RESUMO

To investigate the association between smoking and invasive fungal disease (IFD), we searched MEDLINE and Web of Science for studies published until September 2018. Two authors independently performed study selection and data extraction. Relative risks (RRs) were pooled using random-effects meta-analysis. We included 25 studies (18 171 participants; 2527 IFD cases). The meta-analysis showed an increased risk of IFD in smokers (RR 1.41 [95% confidence interval 1.09-1.81]; P = .008). The risk of IFD was higher in retrospective than in prospective studies (RR 1.93 [1.28-2.92] vs. 1.02 [0.78-1.34]; P = .04), in studies with multivariate adjustment compared to studies with univariate analysis (RR 2.15 [1.27-3.64] vs. 1.15 [0.88-1.51]; P = .06), and in studies published after 2002 (RR 2.08 [1.37-3.15] vs. 0.95 [0.75-1.22]; P = .008); other subgroup characteristics did not significantly influence the association in metaregression. Smoking cessation strategies should be implemented, especially in patients who are already at risk for IFD.

7.
Emerg Infect Dis ; 25(12): 2319-2321, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31742513

RESUMO

We report a case of Aspergillus felis infection in a patient with chronic granulomatous disease who had overlapping features of invasive pulmonary aspergillosis and allergic bronchopulmonary aspergillosis. Identifying the species responsible for aspergillosis by molecular methods can be crucial for directing patient management and selection of appropriate antifungal agents.


Assuntos
Aspergilose/diagnóstico , Aspergilose/etiologia , Aspergillus , Doença Granulomatosa Crônica/complicações , Doença Granulomatosa Crônica/diagnóstico , Adulto , Antifúngicos/uso terapêutico , Aspergilose/tratamento farmacológico , Aspergilose Broncopulmonar Alérgica/diagnóstico , Aspergillus/efeitos dos fármacos , Aspergillus/genética , Biomarcadores , Doença Granulomatosa Crônica/genética , Humanos , Aspergilose Pulmonar Invasiva/diagnóstico , Contagem de Leucócitos , Masculino , Tomografia Computadorizada por Raios X , Resultado do Tratamento
8.
Artigo em Inglês | MEDLINE | ID: mdl-31405852

RESUMO

We report the cases of a 39-year-old woman with chronic lymphocytic leukemia and a 21-year-old man with chronic granulomatous disease treated for cerebral aspergillosis. The patients required radical surgery for infection progression despite adequate isavuconazole plasma concentration or neurological complication. We thus decided to measure the brain isavuconazole concentration. These results suggest that the concentrations of isavuconazole obtained in the infected brain tissue clearly differ from those obtained in the normal brain tissue and the cerebrospinal fluid.


Assuntos
Encéfalo/microbiologia , Doença Granulomatosa Crônica/tratamento farmacológico , Nitrilos/uso terapêutico , Piridinas/uso terapêutico , Triazóis/uso terapêutico , Adulto , Aspergilose/tratamento farmacológico , Aspergilose/microbiologia , Aspergillus fumigatus/efeitos dos fármacos , Aspergillus fumigatus/patogenicidade , Líquido Cefalorraquidiano , Feminino , Doença Granulomatosa Crônica/microbiologia , Humanos , Imagem por Ressonância Magnética , Adulto Jovem
9.
J Fungi (Basel) ; 4(4)2018 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-30562960

RESUMO

Immune deficiency of diverse etiology, including human immunodeficiency virus (HIV), antineoplastic agents, immunosuppressive agents used in solid organ recipients, immunomodulatory therapy, and other biologics, all promote invasive fungal infections. Subsequent voluntary or unintended immune recovery may induce an exaggerated inflammatory response defining immune reconstitution inflammatory syndrome (IRIS), which causes significant mortality and morbidity. Fungal-associated IRIS raises several diagnostic and management issues. Mostly studied with Cryptococcus, it has also been described with other major fungi implicated in human invasive fungal infections, such as Pneumocystis, Aspergillus, Candida, and Histoplasma. Furthermore, the understanding of IRIS pathogenesis remains in its infancy. This review summarizes current knowledge regarding the clinical characteristics of IRIS depending on fungal species and existing strategies to predict, prevent, and treat IRIS in this patient population, and tries to propose a common immunological background to fungal IRIS.

10.
Infect Dis (Lond) ; 50(11-12): 822-830, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30317897

RESUMO

BACKGROUND: Non-typhoidal salmonellosis (NTS) often occurs in children with sickle-cell disease (SCD) and remains a significant cause of mortality in developing countries. However, there is lack of reports on the clinical presentation, outcome and complications of NTS in adults with SCD. METHODS: We performed a chart review between 2006 and 2016 of adults SCD diagnosed with NTS in 3 referral centers monitoring approximately 3500 SCD adults. RESULTS: Twenty-three episodes of NTS were diagnosed among 22 SCD adults. Diagnosis was challenging: 65% (n = 15/23) of patients presented with vaso-occlusive crisis (VOC) and 30% had no fever. Isolated serotypes were: ser. Enteritidis (n = 8), ser. Typhimurium (n = 6), others (n = 3). We identified two patterns of infections: (1) bacteremic NTS (n = 15) with (n = 9) or without secondary foci of infections (n = 6); (2) non-bacteremic NTS with extra-intestinal foci of infection (n = 8), including primary bones/joints infections (n = 5). Half of patients with osteo-articular localization (n = 6/13) had a previous history of osteonecrosis (n = 2) or osteomyelitis (n = 4) at the same site. Morbidity was high, 6 patients (26%) were admitted to the intensive care unit, 14 patients (61%) required RBC transfusion for VOC. Half of the episodes (n = 12) required surgery (n = 10) or interventional radiology (n = 2) to control the infection. One patient presented a relapse of NTS bacteraemia one year after the first episode. CONCLUSIONS: Besides bloodstream infections, clinical presentation of NTS in adults with SCD is non-specific at admission. A triad including bacteraemia, secondary focis of infection and bone localizations was observed in 30% of cases.


Assuntos
Anemia Falciforme/complicações , Bacteriemia/diagnóstico por imagem , Infecções por Salmonella/diagnóstico por imagem , Salmonella/isolamento & purificação , Adolescente , Adulto , Bacteriemia/microbiologia , Bacteriemia/patologia , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/microbiologia , Osso e Ossos/patologia , Feminino , Hospitalização , Humanos , Articulações/diagnóstico por imagem , Articulações/microbiologia , Articulações/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Infecções por Salmonella/complicações , Infecções por Salmonella/microbiologia , Infecções por Salmonella/patologia , Sorogrupo , Tomografia Computadorizada por Raios X , Adulto Jovem
11.
Artigo em Inglês | MEDLINE | ID: mdl-29967027

RESUMO

Voriconazole is the standard treatment for invasive aspergillosis but requires therapeutic drug monitoring to optimize therapy. We report two cases of central nervous system aspergillosis treated with voriconazole. Because of low trough plasma concentrations, we identified gain-of-function mutations in CYP2C19 that were partially responsible for the therapeutic failure of voriconazole. We suggest that systematic voriconazole pharmacogenomic investigation of cerebral aspergillosis be performed to avoid effective therapy delay in this life-threatening disease.


Assuntos
Antifúngicos/uso terapêutico , Aspergilose/tratamento farmacológico , Aspergilose/genética , Sistema Nervoso Central/microbiologia , Voriconazol/uso terapêutico , Adulto , Idoso , Citocromo P-450 CYP2C19/genética , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Mutação/genética , Farmacogenética/métodos
12.
Sci Immunol ; 3(24)2018 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-29907691

RESUMO

Heterozygosity for human signal transducer and activator of transcription 3 (STAT3) dominant-negative (DN) mutations underlies an autosomal dominant form of hyper-immunoglobulin E syndrome (HIES). We describe patients with an autosomal recessive form of HIES due to loss-of-function mutations of a previously uncharacterized gene, ZNF341 ZNF341 is a transcription factor that resides in the nucleus, where it binds a specific DNA motif present in various genes, including the STAT3 promoter. The patients' cells have low basal levels of STAT3 mRNA and protein. The autoinduction of STAT3 production, activation, and function by STAT3-activating cytokines is strongly impaired. Like patients with STAT3 DN mutations, ZNF341-deficient patients lack T helper 17 (TH17) cells, have an excess of TH2 cells, and have low memory B cells due to the tight dependence of STAT3 activity on ZNF341 in lymphocytes. Their milder extra-hematopoietic manifestations and stronger inflammatory responses reflect the lower ZNF341 dependence of STAT3 activity in other cell types. Human ZNF341 is essential for the STAT3 transcription-dependent autoinduction and sustained activity of STAT3.


Assuntos
Regulação da Expressão Gênica/imunologia , Síndrome de Job/genética , Fator de Transcrição STAT3/genética , Fatores de Transcrição/genética , Transcrição Genética/imunologia , Adolescente , Adulto , Diferenciação Celular/genética , Diferenciação Celular/imunologia , Núcleo Celular/metabolismo , Consanguinidade , Citocinas/imunologia , Citocinas/metabolismo , Éxons/genética , Feminino , Genes Recessivos/genética , Genes Recessivos/imunologia , Homozigoto , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Síndrome de Job/sangue , Síndrome de Job/imunologia , Mutação com Perda de Função , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Linhagem , Regiões Promotoras Genéticas/genética , RNA Mensageiro/metabolismo , Fator de Transcrição STAT3/imunologia , Fator de Transcrição STAT3/metabolismo , Células Th17/imunologia , Células Th17/metabolismo , Células Th2/imunologia , Células Th2/metabolismo , Fatores de Transcrição/imunologia , Fatores de Transcrição/metabolismo , Sequenciamento Completo do Exoma , Adulto Jovem , Dedos de Zinco/genética
13.
PLoS Negl Trop Dis ; 11(11): e0006094, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29155816

RESUMO

BACKGROUND: Complex cutaneous and muco-cutaneous leishmaniasis (CL and MCL) often requires systemic therapy. Liposomal amphotericin B (L-AmB) has a strong potential for a solid clinical benefit in this indication. METHODS: We conducted a retrospective analysis of data from a French centralized referral treatment program and from the "LeishMan" European consortium database. All patients with parasitologically proven CL or MCL who received at least one dose of L-AmB were included. Positive outcome was based on ulcer closure as per recent WHO workshop guidelines. RESULTS: From 2008 through 2016, 43 travelers returning from 18 countries (Old World n = 28; New World n = 15) were analyzed with a median follow-up duration of 79 days [range 28-803]. Main clinical forms were: localized CL with one or multiple lesions (n = 32; 74%) and MCL (n = 8; 19%). As per published criteria 19 of 41 patients (46%) were cured 90 days after one course of L-AmB. When the following items -improvement before day 90 but no subsequent follow-up, delayed healing (>3 months) and healing after a second course of L-AmB- were included in the definition of cure, 27 of 43 patients (63%) had a positive outcome. Five patients (MCL = 1; CL = 4) experienced a relapse after a median duration of 6 months [range 3-27] post treatment and 53% of patients (23/43) experienced at least one adverse event including severe hypokalaemia and acute cardiac failure (one patient each). In multivariate analysis, tegumentary infection with L. infantum was associated with complete healing after L-AmB therapy (OR 5.8 IC 95% [1.03-32]) while infection with other species had no impact on outcome. CONCLUSION: In conditions close to current medical practice, the therapeutic window of L-AmB was narrow in travellers with CL or MCL, with the possible exception of those infected with L. infantum. Strict follow-up is warranted when using L-AmB in patients with mild disease.


Assuntos
Anfotericina B/uso terapêutico , Antiprotozoários/uso terapêutico , Leishmaniose Cutânea/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anfotericina B/administração & dosagem , Anfotericina B/efeitos adversos , Antiprotozoários/administração & dosagem , Antiprotozoários/efeitos adversos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Leishmania/classificação , Leishmania/efeitos dos fármacos , Leishmaniose Cutânea/parasitologia , Leishmaniose Mucocutânea/tratamento farmacológico , Leishmaniose Mucocutânea/parasitologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Viagem , Resultado do Tratamento
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